The major cause of death and morbidity in persons with diabetes mellitus is excessive atherosclerosis. The causes of enhanced rates of atherosclerosis and of medial sclerosis in diabetes are poorly understood. Several lines of evidence suggest strongly that abberations of blood lipoproteins have importance in this regard, but previous data in diabetics are conflicting and incomplete. Particularly lacking in diabetes is information on patterns and distributions of specific apolipoproteins and their relationships to the excessive rates of atherosclerosis. Another problem is that detailed studies of apolipoproteins in diabetics have seldom been attended by detailed data collection in these diabetics on the many concomitants of diabetes that may in themselves influence apolipoproteins and atherogenesis (e.g., obesity, antidiabetic therapy, excessive blood pressure, etc). Data have also been sparse on the relationship of apoprotein status to the vascular status of the diabetics under study. Local circumstances are particularly propitious because of the availability of both highly-sophisticated competence for ascertaining the status of serum apolipoproteins in detail using recently developed methods, together with epidemiologic resources for determining in each diabetic subject an array of 150 data items that will help greatly in interpreting the blood lipid data. These will include both items potentially important in causing vascular morbidity (e.g., fatness, blood glucose level, etc) and data on manifestations of atherosclerosis (e.g., electrocardiography, foot blood pressure, etc). In a two-year study detailed analyses of blood lipoproteins, and apoproteins will be performed on 200 diabetics and 100 nondiabetics in each of whom comprehensive epidemiologic observations will be performed concerning their status with respect to both diabetes and vascular disease. Through ongoing grants already funded by NIH, resources already exist for performing about 90% of the epidemiologic work. Funds are requested to support the detailed studies of bloodlipids and for the coordination of these two aspects (lipid analyses and epidemiologic work).